Abstract
Thyroid hormones (TH) are multifunctional mediators that fine-tune several physiological processes, including metabolic rate, digestive function and tissue development via interactions with type II nuclear thyroid hormone receptors (TR). Upon binding of TH, TRs interact specifically with thyroid hormone response elements of target gene promoter regions to regulate their transcription. Earlier studies suggested a correlation between aberrant TR regulation and hepatocellular carcinoma (HCC). THs are involved in a crosstalk between hepatoma and stromal cells, and disruption of TH signaling is associated with tumorigenesis. Previous cDNA microarray analysis of target gene expression following T3 treatment of wild-type TR-expressing hepatoma cells led to the identification of forkhead box M1 (FOXM1) as a factor negatively regulated by T3 and associated with poor prognosis in several cancer types. Increased FOXM1 expression during late stages of HCC was associated with poorer overall and recurrence-free survival in patients with HCC. However, the specific mechanisms underlying FOXM1 activity in liver cancer progression remain to be elucidated. Experiments from the present study showed that TH/TR signaling suppresses FOXM1 mRNA and protein expression. Depletion of FOXM1 induced inhibition of the cell growth rate and a decline in oncogenic cyclin D1, cyclin E and CDK2 expression. Conversely, overexpression of FOXM1 enhanced cell proliferation and expression of oncogenic factors, which was decreased upon FOXM1 depletion. Re-expression of FOXM1 partially rescued suppression of cell proliferation induced by T3. Collectively, the present findings suggest that TH/TR participates in HCC progression via modulation of FOXM1 expression.
Original language | English |
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Pages (from-to) | 1686-1698 |
Number of pages | 13 |
Journal | Oncology Reports |
Volume | 44 |
Issue number | 4 |
DOIs | |
State | Published - 10 2020 |
Bibliographical note
Publisher Copyright:© 2020 Spandidos Publications. All rights reserved.
Keywords
- Forkhead box MI
- Hepatocellular carcinoma
- Prognosis
- Proliferation
- Thyroid hormone
- Thyroid hormone receptor